Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella (MMAF). Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement. Mammalian sperm-associated antigen 17 ( SPAG17 ) encodes a conserved axonemal protein of cilia and flagella, forming part of the C1a projection of the central apparatus, with functions related to ciliary/flagellar motility, skeletal growth, and male fertility. This study investigated two novel homozygous SPAG17 mutations (M1: NM_206996.2, c.829+1G>T, p.Asp212_Glu276del; and M2: c.2120del, p.Leu707*) identified in four infertile patients from two consanguineous Pakistani families. These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa. Quantitative real-time polymerase chain reaction (PCR) of patients' spermatozoa also revealed a significant decrease in SPAG17 mRNA expression, and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella. However, no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients. Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls. Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17 (SPATA17), a component of the C1a projection, and sperm-associated antigen 6 (SPAG6), a marker of the spring layer, revealed disrupted expression of both proteins in the patients' spermatozoa. Altogether, these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme, expanding the phenotypic spectrum of SPAG17 mutations in humans.
Humans ; Male ; Infertility, Male/pathology* ; Sperm Tail/ultrastructure* ; Homozygote ; Microtubule-Associated Proteins/genetics* ; Axoneme/genetics* ; Spermatozoa/ultrastructure* ; Adult ; Mutation ; Sperm Motility/genetics* ; Pedigree ; Microtubules ; Microtubule Proteins/genetics*

This review article classifies chronic myeloid leukemia (CML) based on cytogenetic analyses and different mutations detected in CML patients. The use of advanced technologies, such as karyotyping, fluorescent in situ hybridization, and comparative genomic hybridization, has allowed us to study CML in detail and observe the different biochemical changes that occur in different CML types. This review also highlights the different types of receptor and signaling pathway mutations that occur in CML.

Objective: To investigate the analgesic effect of Boswellia sacra (B. sacra), which could support the Omani traditional uses of frankincense for muscle, stomach, and arthritis pain. Methods: The crude extract, the essential oils and various sub-fractions of the crude methanol extract (each 300 mg/kg of the body weight of the animal) obtained from the resin of B. sacra were administered orally, and were evaluated for their analgesic activities by using two well known models of pain in mice, viz. acetic acid induced writhing test and formalin induced pain test in mice. Results: Of 13 samples, almost all of them were effective at an orally administered dose of 300 mg/kg of the body weight. The acetic acid induced writhes were inhibited in all the three phases with comparable values to the standard drug aspirin (300 mg/kg of body weight) with inhibition of 67.6% in phase I, 66.8% in phase II, and 37.9% in phase III. At the same time, all the tested samples were found effective in both the early and the late phases of formalin test. In formalin test, most of the tested samples showed more inhibitory effects as compared to the standard drug aspirin (300 mg/kg of body weight), which showed 36.2% and 29.6% inhibition in early and late phases respectively. Among the tested samples, the most significant inhibition was produced by Shabi frankincense oil (57.5% in early phase, and 55.6% in late phase). Interestingly, the extracts showed comparable percentage of inhibition to the oil and found in the following order: 60% chloroform. /n-hexane sub-fraction (55.3% in early phase, and 66.7% in late phase), and 70% chloroform. /n-hexane sub-fraction (59.6% in early phase, and 63.0% in late phase). Conclusions: The present study provided the scientific justification about the analgesic properties of the essential oils, extract, and various sub-fractions obtained from the resin of B. sacra, thus validating its use in traditional folk medicines and other products; and hence supporting the development in the analgesic properties of bioactive natural substances.